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Blood, 15 August 2001, Vol. 98, No. 4, pp. 1135-1141
IMMUNOBIOLOGY
Th2 polarization by Der p 1-pulsed monocyte-derived dendritic
cells is due to the allergic status of the donors
Hamida Hammad,
Anne-Sophie Charbonnier,
Catherine Duez,
Alain Jacquet,
Geoffrey A. Stewart,
André-Bernard Tonnel, and
Joël Pestel
From Unité INSERM U416, IFR 17, Institut Pasteur
de Lille, France; Department of Applied Genetics, Université
Libre de Bruxelles, Gosselies, Belgium; Department of Microbiology,
University of Western Australia, Nedlands, Perth, Australia; and
Département de Pneumologie, Hôpital A. Calmette, CHRU de
Lille, Lille Cedex, France.
The polarization of the immune response toward a Th2 or a Th1
profile can be mediated by dendritic cells (DCs) following antigen presentation and interaction with T cells. Costimulatory molecules such
as CD80 and CD86 expressed by DCs, the polarizing cytokine environment
during DC-T-cell interaction, and also the nature of the antigen are
critical in the orientation of the immune response. In this study, the
effect of the cysteine protease Der p 1, one of the major allergens of
the house dust mite Dermatophagoides pteronyssinus, on
these different parameters was evaluated comparatively on
monocyte-derived DCs obtained from healthy donors, from
pollen-sensitive patients, or from patients sensitive to
Dermatophagoides pteronyssinus. Results showed that Der p 1 induced an increase in CD86 expression only on DCs from house dust
mite-sensitive patients. This was also associated with a higher
capacity to induce T-cell proliferation, a rapid increase in the
production of proinflammatory cytokines, tumor necrosis factor- and
interleukin (IL)-1 , and the type 2 cytokine IL-10. No changes in the
release of IL-12 p70 were induced by Der p 1. Finally, purified T cells
from house dust mite-sensitive patients stimulated by autologous Der p
1-pulsed DCs preferentially produced IL-4 rather than interferon- .
These effects were abolished in the presence of the inactive precursor of Der p 1 (ProDer p 1). Taken together, these data suggest that DCs
from house dust mite-sensitive patients, in contrast to DCs from
healthy donors and from pollen-sensitive patients, exposed to Der p 1 play a pivotal role in the enhancement of the Th2 response associated
with the allergic reaction developed in response to house dust mite exposure.
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